Expression of C/EBPβ in myeloid progenitors during sepsis promotes immunosuppression.
Expression of C/EBPβ in myeloid progenitors during sepsis promotes immunosuppression.
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DOI：
10.1016/j.molimm.2017.09.008
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发表时间：
2017-11
影响因子：
3.6
通讯作者：
El Gazzar M
中科院分区：
文献类型：
--
作者：
Dai J;Kumbhare A;Youssef D;Yao ZQ;McCall CE;El Gazzar M
脓毒症诱导的骨髓源性抑制细胞（MDSC）有助于脓毒症相关的免疫抑制。我们报道了CCAAT增强子结合蛋白C/EBPβ激活microRNA（miR）-21和miR-181 b表达，从而诱导转录因子NFI-A支持脓毒症小鼠骨髓和脾脏中MDSC的产生和扩增。在这里，我们使用髓系中缺乏C/EBPβ的条件性敲除小鼠模型，发现在没有C/EBPβ的情况下，髓系祖细胞不能表达miR-21或miR-181 b，并且C/EBPβ在C/EBPβ缺陷的髓系祖细胞中的异位表达激活了这两种miRNA的表达。此外，C/EBPβ重建的骨髓细胞表达IL-10并降低T细胞增殖和功能，与表达C/EBPβ的对照MDSC相似。在败血症小鼠的C/EBPβ缺陷型髓系祖细胞中外源性表达miR-21和miR-181 b产生了类似的结果。值得注意的是，NF-kB MDSC生成途径的NFI-A依赖性反式激活在来自脓毒症小鼠的C/EBPβ缺陷型骨髓祖细胞中逆转。总之，这些结果支持降低C/EBPβ表达可防止脓毒症小鼠中MDSC生成并降低免疫抑制，为脓毒症治疗提供了靶点。
Sepsis-induced myeloid-derived suppressor cells (MDSCs) contribute to immunosuppression associated with sepsis. We reported that the CCAAT enhancer-binding protein C/EBPβ activates microRNA (miR)-21 and miR-181b expressions, which induce transcription factor NFI-A to support the generation and expansion of MDSCs in the bone marrow and spleens of septic mice. Here, using a conditional knockout mouse model lacking C/EBPβ in the myeloid lineage, we find that without C/EBPβ, myeloid progenitor cells could not express miR-21 or miR-181b, and ectopic expression of C/EBPβ in the C/EBPβ-deficient myeloid progenitors activated the expression of the two miRNAs. Moreover, C/EBPβ-reconstituted myeloid cells expressed IL-10 and reduced T cell proliferation and function, similar to control MDSCs that express C/EBPβ. Exogenous expression of miR-21 and miR-181b in the C/EBPβ-deficient myeloid progenitors from septic mice produced similar results. Notably, NFI-A-dependent transactivation of NF-kB MDSC generating pathway was reversed in the C/EBPβ-deficient myeloid progenitors from septic mice. Together, these results support that decreasing C/EBPβ expression prevents MDSC generation and decreases immunosuppression in septic mice, providing a target for sepsis treatment.
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DOI：
10.1186/cc10112
发表时间：
2011
期刊：
Critical care (London, England)
影响因子：
--
作者：
Guignant C;Lepape A;Huang X;Kherouf H;Denis L;Poitevin F;Malcus C;Chéron A;Allaouchiche B;Gueyffier F;Ayala A;Monneret G;Venet F
通讯作者：
Venet F
脓毒症病理生理学、慢性危重疾病、持续性炎症-免疫抑制和分解代谢综合征。
影响因子：
8.8
作者：
Mira JC;Gentile LF;Mathias BJ;Efron PA;Brakenridge SC;Mohr AM;Moore FA;Moldawer LL
通讯作者：
Moldawer LL
影响因子：
120.7
作者：
Boomer, Jonathan S.;To, Kathleen;Chang, Kathy C.;Takasu, Osamu;Osborne, Dale F.;Walton, Andrew H.;Bricker, Traci L.;Jarman, Stephen D., II;Kreisel, Daniel;Krupnick, Alexander S.;Srivastava, Anil;Swanson, Paul E.;Green, Jonathan M.;Hotchkiss, Richard S.
通讯作者：
Hotchkiss, Richard S.
DOI：
10.1038/nri3552
发表时间：
2013-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.3
作者：
El Gazzar, Mohamed;Yoza, Barbara K.;McCall, Charles E.
通讯作者：
McCall, Charles E.